P372: DISMAL OUTCOMES OF PATIENTS WITH RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA AFTER FAILURE OF BOTH INOTUZUMAB OZOGAMICIN AND BLINATUMOMAB
Authors: W. Macaron, E. Jabbour, M. Konopleva, F. Ravandi, N. Jain, G. Issa, T. Kadia, K. Sasaki, P. Kebriaei, M. Yilmaz, P. Thompson, K. Takahashi, H. Abbas, W. Wierda, R. Garris, H. Kantarjian, N. Short
Journal: HemaSphere (2022)

Background: The development of novel monoclonal antibodies such inotuzumab ozogamicin (INO) and blinatumomab (Blina) results in superior response rates and survival in patients (pts) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). However, outcomes of pts after failure of both INO and Blina are not well-established, and effective treatment options for these pts are limited. Aims: To determine response rates to subsequent therapies and overall survival (OS) in pts with R/R Philadelphia chromosome (Ph)-negative B-cell ALL after failure of both INO/Blina. Methods: We conducted a retrospective analysis of outcomes in adult pts with Ph-negative B-cell ALL who relapsed or were refractory to both INO/Blina, at least one of which given as salvage therapy. Results: The baseline characteristics of the 65 pts included are shown in Table 1. Of 29 pts with paired flow cytometry for CD19 and CD22 prior to receipt of either INO/Blina, 4 pts (14%) lost CD19 expression and 3 pts (10%) lost CD22 expression at time of INO/Blina failure. After INO/Blina failure, 54 pts (83%) received subsequent therapy, with a median of 2 therapies (range, 1-6). Of 53 evaluable pts, 16 pts (30%) achieved CR/CRi with the first salvage therapy received after INO/Blina failure (CR=9%, CRi=21%), and 22 pts (42%) achieved CR/CRi with at least one salvage therapy (CR=17%, CRi=25%). Of the 22 responders, 16 pts (73%) achieved measurable residual disease (MRD) negativity by flow cytometry (sensitivity=0.01%) at best response. Nine responses (41%) were achieved with an investigational drug/regimen and 13 (59%) were achieved with commercial agent(s). Among 54 pts who received at least one subsequent therapy, 12 pts (22%) received CAR T-cells, and 9 pts (17%) proceeded to hematopoietic stem cell transplant (HSCT). With a median follow-up of 22.3 months, the median OS from the time of INO/Blina failure for the entire population was 3.8 months, and the 1-year OS was 22% (figure 1A). Median relapse-free survival (RFS) was 3.5 months, with a 1-year RFS of 12%. Median duration of response (DOR) to subsequent therapy was 5.0 months, with a 1-year DOR of 17%. Median OS from INO/Blina failure in pts who received salvage therapy compared to those who did not were 4.7 months and 1.4 months, respectively (figure 1B). In the 9 pts who underwent HSCT, 2 (22%) are still alive and in continuous remission. The median OS from time of HSCT was 13.4 months, and the 1-year post-HSCT OS was 59%. In the 12 pts who received CAR-T cells as a subsequent therapy, 6 (50%) responded and 2 were bridged directly to HSCT. The median OS from time of CAR T-cell therapy was 3.9 months, and the 1-year OS was 36%. Outcomes of pts who received both INO and Blina as salvage therapy (n=50), excluding those who received 1 of these agents in the frontline or MRD setting, were also analyzed. Median OS from the time of INO/Blina failure was 2.6 months. Thirty-nine (78%) of these 50 pts received subsequent therapy after INO/Blina failure. Of 38 evaluable pts, 15 pts (39%) achieved CR/CRi with at least one subsequent salvage therapy (CR=13%, CRi=26%). Median RFS and OS in pts who underwent subsequent therapy were 5.9 months and 3.9 months, respectively. Image:Summary/Conclusion: This study highlights the very poor outcomes of pts with R/R B-cell ALL after failure of both INO/Blina. For pts who respond to subsequent salvage therapy, a consolidative approach with SCT may improve outcomes. These data provide a historical reference for expected outcomes that may serve as a benchmark for the evaluation of novel drugs and combinations in the setting of INO/Blina failure.